Diabetic Kidney Disease Linked to Reduced Mitochondrial Function

Significant differences in the levels of 12 metabolites between patients with diabetes mellitus and chronic kidney disease (CKD) and others indicate that mitochondria suppression is a fundamental characteristic of diabetes-related kidney disease.

Diabetic kidney disease is the leading cause of end-stage renal disease, but few biomarkers of this condition are available, wrote Kumar Sharma, MD, Director of the Center for Renal Translational Medicine at University of California San Diego (UCSD), and colleagues reported online ahead of print in the Journal of the American Society of Nephrology.

Dr. Sharma's team sought to identify such biomarkers by using gas chromatography-mass spectrometry to quantify 94 urine metabolites in three screening and validation cohorts:

Patients with diabetes mellitus and CKD (DM+CKD)

Patients with diabetes mellitus but not CKD (DM–CKD)

Healthy controls

Compared with levels in healthy controls, 13 metabolites were significantly reduced in the DM+CKD group, and 12 of the 13 metabolites remained significant when compared with the DM–CKD group. Analysis of bioinformatics data indicated that 12 of the 13 differently expressed metabolites are linked with mitochondrial metabolism and suggested suppression of mitochondrial activity in persons with DM+CKD.

“This work provides strong evidence that reduced mitochondrial function is a dominant feature of human diabetic kidney disease,” Dr. Sharma said in a UCSD statement.

The researchers found that a specific cellular pathway likely plays a key role to reduce mitochondrial function and content, meaning that new treatments that restore and increase mitochondrial function and content could ameliorate or even arrest CKD.